Microtubule-associated proteins (MAPs) have previously been shown to interact primarily with microtubules both in vitro and in situ. However, we have recently documented the association of one MAP, tau, with ribosomes in neural cells as well as with microtubules. Additionally, analysis of the bovine tau gene sequence indicates the existence of, as yet, undescribed isoforms of this protein encoded in EXON 14 that may impart DNA binding properties to tau. We have shown that both tau and a MAPlB-like protein localize in nucleoli in primate cells in culture (see Section C). Hence, MAP1B and tau appear to be multifunctional molecules that are involved in nuclear processes as well as in microtubule biology. We hypothesize that targeting of these MAPs to either microtubules in specific neural compartments in the brain or to the nucleus in rapidly dividing cells involves transcriptional and/or translational modifications that uniquely adapt a particular MAP species to its eventual segregation and function. This hypothesis will be tested by (1) defining chemical and functional differences between nuclear and microtubule-derived tau and MAP1B, (2) elucidating the biology of nuclear tau and the MAPlB-like polypeptide, and by (3) determining whether the nuclear tau polypeptides represent unique, DNA-binding isoforms of tau.